Interleukin‐2‐mediated CD4 T‐cell activation correlates highly with effective serological and T‐cell responses to SARS‐CoV‐2 vaccination in people living with HIV

Abstract

People living with HIV (PLWH) despite having an appreciable depletion of CD4+ T‐cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T‐cell responses in PLWH receiving anti‐retroviral therapy stratified on CD4+ counts as PLWH‐high (CD4 ≥ 500 cells/mm3) and PLWH‐low (<500 cells/mm3). Responses were assessed longitudinally before the first vaccination (T0), 1‐month after the first dose (T1), 3‐months (T2), and 6‐months (T3) after the second dose. Expectedly, both PLWH‐high and ‐low groups developed similar serological responses after T2, which were also non‐significantly different from age and vaccination‐matched HIV‐negative controls at T3. The immunoglobulin G titers were also protective showing a good correlation with angiotensin‐converting enzyme 2‐neutralizations (R = 0.628, p = 0.005). While surface and intracellular activation analysis showed no significant difference at T3 between PLWH and controls in activated CD4+CD154+ and CD4+ memory T‐cells, spike‐specific CD4+ polyfunctional cytokine expression analysis showed that PLWH preferentially express interleukin (IL)‐2 (p < 0.001) and controls, interferon‐γ (p = 0.017). CD4+ T‐cell counts negatively correlated with IL‐2‐expressing CD4+ T‐cells including CD4+ memory T‐cells (Spearman ρ: −0.85 and −0.80, respectively; p < 0.001). Our results suggest that the durable serological and CD4+ T‐cell responses developing in vaccinated PLWH are associated with IL‐2‐mediated CD4+ T‐cell activation that likely compensates for CD4+ T‐cell depletion in PLWH.